Inhibition of intercellular communication in smooth muscle cells of humans and rats by low density lipoprotein, cigarette smoke condensate and TPA.
Inhibition by tumor promoting chemicals of intercellular communication via gap junctions may be important in carcinogenesis. In order to investigate the possible role of gap junctional intercellular communication in atherogenesis, we examined the effect of known inhibitors of intercellular communication, 12-O-tetradecanoylphorbol-13-acetate (TPA) and cigarette smoke condensate (CSC), and low density lipoproteins (LDL) and high density lipoproteins (HDL) on cellular communication in smooth muscle cells of human and rat by the microinjection-dye transfer technique. When lucifer yellow CH solution is injected into a cell, the average numbers of human and rat smooth muscle cells that become fluorescent is about 22 and 6, respectively. The tumor promoter (TPA) almost completely blocked gapjunctional communication between smooth muscle cells at 100 ng/ml after 4 h exposure. LDL and CSC were able to inhibit intercellular communication in human and rat cells in a dose-dependent manner up to 60%. LDL-pretreatment of human smooth muscle cells did not affect inhibition of intercellular communication, which suggests that this effect is mainly non-receptor mediated. HDL did not influence junctional communication. The results indicate that inhibition of intercellular communication may also contribute to the pathogenesis of atherosclerotic lesions, such as plaques.
Zwijsen
R M
RM
Department of Toxicology, Agricultural University, Wageningen, The Netherlands.
de Haan
L H
LH
Oosting
J S
JS
Pekelharing
H L
HL
Koeman
J H
JH
D000818:Animals; D002450:Cell Communication / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005456:Fluorescent Dyes; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects / Q000502:physiology; D007546:Isoquinolines; D008075:Lipoproteins, HDL / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010947:Plants, Toxic; D051381:Rats; D012906:Smoke; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014026:Nicotiana
D005456:Fluorescent Dyes; D007546:Isoquinolines; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D012906:Smoke; C017475:lucifer yellow; D013755:Tetradecanoylphorbol Acetate